Dose Escalation Upper Limb Rehabilitation in Stroke

Finding the Optimal Session Length of Upper Limb Rehabilitation of People With Moderate to Severe Upper Limb Sensorimotor Impairments After Acute Stroke: A Dose Escalation Study

A phase 1, single-ascending dose clinical trial will be conducted. This study will be designed to test increasing doses of multimodal exercise in successive cohorts of six participants (cumulative 3 + 3 design)[22] (Figure 1).

Maximum dose is reached when two or more participants experience DLT. DLT, dose-limiting tolerance.

The 'dose' will be defined as the ability to reach a fixed maximal level of exercise (type, duration (including session length) in the first two weeks post-stroke without experiencing dose-limiting tolerance (DLT). DLT thresholds will be based on failure to completeshould be less than 80% of prescribed 3-day rehabilitation dose due to pain, rate of perceived exertion, fatigue, or effort required.

Rehabilitation and measurement sessions will be held at either at the Stroke or Geriatric Units at Campus Sint-Jan, Genk or at the rehabilitation unit at Sint-Barbara, Lanaken and Cliniques Saint-Luc with medical services on site. All participants will be monitored for fatigue and pain pre, during and at post-intervention daily. The researchers (PI of project [Dr Peter Hallet, ZOL] Postdoctoral Researcher [Dr Lisa Tedesco Triccas, UHasselt] and PhD/Masters Students [UHasselt) will conduct the clinical tests and will conduct the rehabilitation program.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Other: upper limb rehabilitation

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. a first-ever unilateral, diagnosed stroke by a neurologist as defined by the World Health Organisation,
2. been admitted to the acute hospital for rehabilitation,
3. UL hemiparesis or hemiplegia with a ≥ trace of muscle contraction (≥grade 1 at wrist extensors measured by the MRC Scale and severely motor affected by score of 2 or 3 on item number 5 on the NIH Stroke Scale (NIHSS),
4. the age of > 18 years and (e) the ability to provide informed consent.

Exclusion Criteria:

1. other neurological impairments that could interfere with the protocol such as multiple sclerosis and Parkinson's
2. serious communication, cognitive and language deficits which might hamper the assessment (score of >1 on the command item of the NIHSS).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: participants with acute stroke; (a) a first-ever unilateral, diagnosed stroke by a neurologist as defined by the World Health Organisation, (b) been admitted to the acute hospital for rehabilitation, (c) Upper limb hemiparesis or hemiplegia with a trace of muscle contraction:≥grade 1 at shoulder (abductors or elevators) or wrist/finger extensors measured by the MRC Scale and a score of <61 on the Motricity Index and severely motor affected by score of 2 or 3 on item number 5 on the NIH Stroke Scale (NIHSS)[24], (d) the age of > 18 years and (e) the ability to provide informed consent.

Other: upper limb rehabilitation; the intervention consisting of two components: a) Upper limb training protocol; b) Technology-assist training.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fugl-Meyer Assessment of Motor Recovery after Stroke	a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226.	baseline
Fugl-Meyer Assessment of Motor Recovery after Stroke	a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226.	day 6
Fugl-Meyer Assessment of Motor Recovery after Stroke	a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226.	day 9
Fugl-Meyer Assessment of Motor Recovery after Stroke	a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226.	day 12
Fugl-Meyer Assessment of Motor Recovery after Stroke	a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226.	day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 3
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 4
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 5
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 6
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 7
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 8
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 9
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 10
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 11
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 12
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 13
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 14
Motricity index	Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength.	day 15
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 3
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 4
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 5
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 6
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 7
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 8
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 9
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 10
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 11
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 12
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 13
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 14
Visual Analog Scale of Fatigue (VAS-f)	The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10).	day 15
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 3
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 4
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 5
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 6
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 7
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 8
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 9
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 10
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 11
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 12
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 13
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 14
Borg RPE Scale	Measurement of physical activity intensity (6 to 20 scale)	day 15
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 3
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 4
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 5
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 6
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 7
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 8
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 9
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 10
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 11
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 12
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 13
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 14
Numeric rating scale pain	The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")	day 15

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: Ziekenhuis Oost-Limburg
• Investigators: Study Chair: Lisa Tabone, dr., Hasselt University; Principal Investigator: Peter Feys, prof. dr., Hasselt University

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Actual): May 27, 2024
• Study Completion (Actual): May 27, 2024

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 21, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 27, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: DOMINO-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No